The glucokinase (GK) is an important member of the hexose kinase family, of which the basic biological activity is to catalyze the phosphorylation of glucose. The human glucokinase-encoding gene is located at the short arm of Chromosome 7 and comprises ten exons. The GK consists of 465 amino acids, is present specifically in mature hepatocytes and islet beta-cells, and is involved in many of key steps in glycometabolism and the secretion of insulin.
At present, it has been shown that the intensity in the in vivo insulin secretion response is proportional to the metabolic rate for glucose in insulin beta-cells. Thus, the enzyme that controls the rate of glucose influx into cells is considered as a glucose sensor regulating insulin release, and the GK is the glucose sensor in islet beta-cells. When transferred into a beta-cell through transporter 2, glucose is phosphorylated under the action of the glucokinase and introduced into the glycolytic pathway to give ATP, the amount of which is proportional to the amount of glucose introduced into the beta-cell. ATP can shut down the potassium ion channel on the plasma membrane of the beta-cell, leading to depolarization, which in turn results in calcium ion influx and eventually secretion of insulin. Since the activity of GK is controlled directly or indirectly by glucose concentration in blood, alteration in the metabolic rate for glucose within the beta-cell may regulate the secretion of insulin. Moreover, as the enzyme can also control the blood glucose concentration by facilitating synthesis of hepatic glycogen and catalyzing conversion of glucose into glucose-6-phosphate, an abnormality of GK activity plays a key role in occurrence and development of disturbances of carbohydrate metabolism.
It was found by some investigations that in patients and some animal models (e.g., fasting rats) suffering from type 2 diabetes mellitus, the GK activity in hepatocytes from rats with type 2 diabetes mellitus induced by high-fat diet is significantly reduced as compared to the normal control.